Understanding the biology of Foxp3+ CD8+ regulatory T cells and their potential role in multiple sclerosis

CD4+Foxp3+ regulatory T-cells (Tregs) are the most well characterised suppressive cell type in the immune system, with potent roles in suppressing autoimmunity. By contrast, despite expressing the same master transcription factor, very little is known about CD8+Foxp3+ Tregs. Recent discoveries from our lab, and the lab of our collaborator Adrian Liston, have begun to shed light on these cells, revealing their significant yet overlooked role in immune regulation. Our work has shown that these cells are found are found within B-cell zones of lymphoid organs, suggesting a unique interaction between these cell types. They are also found in significant numbers in human non-lymphoid tissues, indicating their broader role in immune responses.

This project aims to further explore the biology of CD8+Tregs, focusing on their potential role in multiple sclerosis (MS), an autoimmune, demyelinating disorder of the central nervous system. The study will involve detailed characterisation of CD8+ Tregs in healthy individuals and MS patients, spatial analysis of their presence in brain tissue, TCR sequence analysis, and functional testing in human brain slices and mouse models of MS. The overall goal of the project is to better understand the role of CD8+ Tregs in immune regulation and assess their potential as a therapeutic target in MS.